This revised application is responsive to PAR-08-147 (reissue of PAR-06-293), "Quick-Trials for Imaging and Image-Guided Interventions: Exploratory Grants (R21)". The proposed research is a feasibility study that is organ specific and is aimed at determining the ability of a dedicated breast computed tomography system (herein referred to as breast CT system) to visualize lesions. Superposition of breast structures in mammography may result in missed cancers due to 'masking'effect, or may mimic the presence of a lesion resulting in additional imaging or biopsy. Computed Tomographic (CT) Imaging of the breast can overcome this superposition problem, and provide much improved contrast, thus improving detectability. Further, CT imaging of the breast can be performed with no physical compression of the breast, alleviating patient discomfort. It can provide for 3-D lesion morphology, which could serve as a diagnostic indicator, and for better quantitative assessment of breast glandular content, a likely risk factor for breast cancer. This research is to demonstrate that image quality improvements achieved with advanced image processing approaches could improve lesion visualization and provide for better delineation of its margins, using a three-dimensional (3-D) breast imaging system with isotropic voxel size. Improved visualization of lesions and its margins would improve the confidence to determine malignancy and could potentially improve detection. Determination of lesion margins and lesion volume are also necessary for surgical planning and for accurate monitoring and early determination of the effectiveness of therapeutic agents and methods. The research plan includes studies to determine the ability of the dedicated clinical prototype breast CT system to visualize lesions;to determine if the 3-D morphology provides for improved determination of malignancy;to determine if quantitative CT numbers can provide for improved confidence to determine malignancy;and to obtain volumetric estimates of breast density, a likely risk factor for breast cancer. The results from this study will allow us to better define the role of a dedicated 3-D cone-beam flat-panel CT system in breast cancer and will allow us to determine the effectiveness of image processing approaches for improved clinical image quality. A well- designed dedicated breast CT system with advanced image processing techniques can serve as a platform technology for screening and diagnostic imaging, implant imaging, 3-D presurgical planning, monitoring preoperative treatment, and guidance in minimally invasive surgery. PUBLIC HEALTH RELEVANCE: Volumetric 3-D imaging with a dedicated breast CT system has the potential to be an effective tool for monitoring therapeutic treatments and can overcome the tissue superposition problem in mammography, which results in missed cancers and unnecessary recall of the patient for additional imaging. In this research, we propose to conduct a clinical feasibility study with a prototype breast CT system and develop and evaluate methods to improve contrast that could result in improved detection, diagnosis, and management of breast cancer.